Chiale Pablo A, Garro Hugo A, Schmidberg Jorge, Sánchez Rubén A, Acunzo Rafael S, Lago Manuel, Levy Gabriela, Levin Mariano
Division of Cardiology, Ramos Mejía Hospital, Buenos Aires, Argentina.
Heart Rhythm. 2006 Oct;3(10):1182-6. doi: 10.1016/j.hrthm.2006.06.011. Epub 2006 Jun 15.
The mechanisms underlying inappropriate sinus tachycardia are not fully known. An autonomic imbalance seems to play a role, but no attempts have been made to investigate a relationship between this arrhythmia and the antiautonomic membrane receptor antibodies found in other heart disorders and arrhythmias.
The purpose of this study was to investigate the prevalence and the functional and biochemical effects of circulating antiautonomic receptor antibodies in patients with inappropriate sinus tachycardia.
We studied 21 patients with inappropriate sinus tachycardia and 15 healthy volunteers. The chronotropic effects of the IgG fractions (also of affinity-purified anti-beta1 adrenergic receptor antibodies in selected cases) were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The effects of the IgG fractions from five patients and five healthy volunteers on cAMP production were evaluated in COS-7 cells transfected with genes encoding for beta1 or beta2 adrenergic receptor.
The IgG fractions from patients with inappropriate sinus tachycardia exerted a positive chronotropic action with a high prevalence of anti-beta receptor antibodies (52%) and induced a clear-cut and long lasting increment of cAMP. No anti-M2 cholinergic receptor antibodies were found. The IgG fractions from healthy volunteers did not contain antiautonomic receptor antibodies.
Our results suggest, for the first time, a link between inappropriate sinus tachycardia and circulating anti-beta adrenergic receptor antibodies that induce a persistent increment in cAMP production. This finding offers new insight into the physiopathology of inappropriate sinus tachycardia with potential therapeutic consequences.
不适当窦性心动过速的潜在机制尚未完全明确。自主神经失衡似乎起了一定作用，但尚未有人尝试研究这种心律失常与在其他心脏疾病和心律失常中发现的抗自主神经膜受体抗体之间的关系。
本研究旨在调查不适当窦性心动过速患者循环抗自主神经受体抗体的患病率及其功能和生化效应。
我们研究了21例不适当窦性心动过速患者和15名健康志愿者。在接触阿托品和普萘洛尔前后，评估IgG组分（在选定病例中还包括亲和纯化的抗β1肾上腺素能受体抗体）对培养心肌细胞的变时作用。在转染了编码β1或β2肾上腺素能受体基因的COS-7细胞中，评估了5例患者和5名健康志愿者的IgG组分对环磷酸腺苷（cAMP）产生的影响。
不适当窦性心动过速患者的IgG组分具有正性变时作用，抗β受体抗体的患病率较高（52%），并诱导cAMP明显且持久地增加。未发现抗M2胆碱能受体抗体。健康志愿者的IgG组分不含抗自主神经受体抗体。
我们的结果首次表明，不适当窦性心动过速与循环抗β肾上腺素能受体抗体之间存在联系，这些抗体可导致cAMP产生持续增加。这一发现为不适当窦性心动过速的生理病理学提供了新的见解，并具有潜在的治疗意义。
